PROJECT SUMMARY ABSTRACT Under the parent grant, our recent longitudinal findings of accelerated aging of selective brain structures in alcohol-dependent men and women together with signs of premature aging of hippocampal volumes lead to the speculation that that the incidence of accelerated cognitive and mnemonic decline will ensue. Aging itself is the strongest predictor of mild cognitive decline (MCI), which can herald unrelenting tau- based and non-tau-based dementias. A controversy that remains unresolved, however, centers on whether alcohol dependence results in classical, irreversible dementia and whether alcohol-related cognitive and brain structural declines are precursors to Alzheimer's Disease (AD) per se or form part of an Alzheimer's Disease Related Dementia (ADRD) spectrum. It is timely to address these controversies given the aging of the population, increased drinking in the elderly, and the substantial incidence of tau- based dementias. Within Specific Aim 2 of the parent grant is the use of MR neuroimaging to assess the integrity of limbic system structures and tests of component processes of memory to assess functional correlates of identified volume deficits in Alcohol Use Disorder (AUD). Thus, the supplemental work proposed falls within the scope of the active award and extends the work to incorporate acquisition procedures and hippocampal subfield analyses, which had not been fully validated at the submission of the current proposal. Since the submission of the parent application, analysis of a central limbic structure, the hippocampus, has been substantially enhanced especially when combined with use of a 32-channel head coil and the 6.01 version of FreeSurfer automated segmentation of high-resolution MR images of the hippocampus. We have now implemented these procedures in our parent grant work, have developed the analysis pipeline, and are poised to extend our investigations to MCI and ADRD. Specifically, characterization of the profile of hippocampal subfield volume deficits and their relation to cognitive deficits in AUD compared to MCI may provide a biological marker to distinguish the two conditions. Success with this supplemental would provide a unique opportunity to address a common yet heretofore unanswered question whether AUD is associated with or accelerates the cognitive decline and its substrates of MCI and ADRD. An added feature of the supplement would be to advance our work in AUD and its cognitive, motor, and focal brain structural sequelae. SUPPLEMENTAL SPECIFIC AIM Compare profiles of sparing and loss of hippocampal subfield volumes in MCI, AUD, and controls.